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Biomedical subjects

C R Gregg

Publications and source records attributed to C R Gregg.

At least 19 recordsLinked to original sources
PubMed1999

Drug interactions and anti-infective therapies.

Drug interactions are an important and often underappreciated cause of adverse clinical outcomes. This review considers the mechanisms for several clinically important drug interactions that involve the major classes of anti-infective agents. This approach is intended to complement the use of text-based references and computer databases so that physicians and pharmacists can avoid prescribing and dispensing drugs that have adverse interactions.

Administration, Oral↗
PubMed1999

Gonococcal infection of human fallopian tube mucosa in organ culture: relationship of mucosal tissue TNF-alpha concentration to sloughing of ciliated cells.

BACKGROUND AND OBJECTIVES: An experimental model consisting of gonococcal infection of human fallopian tube mucosa in organ culture has proven useful in studying the molecular pathogenesis of acute gonococcal salpingitis and postsalpingitis sequelae. Gonococcal infection of human fallopian tube mucosa in organ culture results in the sloughing of ciliated epithelial cells from the mucosa. This damage to the mucosa can be quantified on fallopian tube pieces by an assay of the percent of the periphery that has ciliary activity (PPCA) remaining at specific time points after infection. Although assay of the PPCA has been quite valuable, it is labor-intensive, somewhat subjective, and requires that the observers have training and experience. A more practical assay for genital mucosal damage is desirable for further investigations that employ the fallopian tube experimental model. Gonococcal infection of fallopian tube mucosa in organ culture also results in the production of easily quantified tumor necrosis factor-alpha (TNF-alpha) by the mucosa. Furthermore, treatment of the organ cultures with recombinant human TNF-alpha (rHuTNFalpha) alone also causes sloughing of ciliated cells from the mucosa. These findings strongly suggest that TNF-alpha is a mediator of the mucosal damage that attends gonococcal infection. GOALS OF THE STUDY: To determine: (1) whether the PPCA values and the TNF-alpha concentrations in fallopian tube mucosal tissues correlate closely enough to allow prediction of the PPCA from a measurement of the mucosal tissue TNF-alpha concentration; and (2) whether the correlation of the TNF-alpha mucosal tissue concentration with the sloughing of ciliated cells (measured by the PPCA) supports the hypothesis that induction of TNF-alpha by gonococcal infection, with resultant sloughing of ciliated cells, is likely to be a major pathogenic mechanism of gonococcal salpingitis and might mediate postsalpingitis infertility and ectopic pregnancy. STUDY DESIGN: A metaanalysis was performed on studies from three research groups (two laboratories in the United States and one in the United Kingdom, using identical techniques for quantifying the PPCA, TNF-alpha, or both. RESULTS: There was a close and statistically significant correlation between the TNF-alpha mucosal tissue concentration and the proportion of ciliated cells lost from the mucosa as measured by the PPCA (r = 0.95, p < 0.001). Therefore, as the mucosal tissue concentration of endogenous TNF-alpha increased, the loss of ciliated cells from the epithelium increased proportionately. CONCLUSIONS: During gonococcal infection of human fallopian tube mucosa in organ culture, the mucosal tissue concentration of TNF-alpha can be used to predict the PPCA, and therefore, the extent of mucosal damage. This finding should facilitate studies of the molecular pathogenesis of infectious diseases involving human genital mucosa. Further, the close correlation of mucosal TNF-alpha concentration with genital mucosal damage, evaluated by the PPCA, supports the hypothesis that induction of the proinflammatory cytokine, TNF-alpha, by gonococcal infection, with resultant inflammation and sloughing of ciliated cells, is an important pathogenic mechanism of gonococcal salpingitis and may mediate postsalpingitis infertility and ectopic pregnancy as well.

Cilia↗
PubMed1990

The evolutionary watershed of susceptibility to gonococcal infection.

Gonococci do not cause genital infection in any convenient experimental animal, but all too easily cause genital infection in humans. To determine the 'evolutionary watershed' of gonococcal infections (the point on the evolutionary tree at which susceptibility to gonococcal infection begins) we extended previous studies of the interaction of gonococci with animal oviduct mucosa to include chimpanzees and baboons. Gonococci attached to, damaged, and invaded the oviduct (fallopian tube) mucosa of chimpanzees (which are apes) but not the oviduct mucosa of baboons (which are monkeys). Thus, the pattern of gonococcal infection in chimpanzees was identical to that in humans, whereas the pattern in baboons was like that in other animals. These studies indicate that the point in evolution at which susceptibility to gonococcal infection commences is between baboons and chimpanzees (or between monkeys and apes). Susceptibility to gonococcal disease appears to require the presence on genital epithelial cells of receptors for gonococcal ligands such as pili, receptors for gonococcal lipopolysaccharide, or both. The physiological role of these receptors may be to interact with more useful, as yet unidentified molecules.

Animals↗
PubMed1987

Treatment of cryptococcal meningitis with combination amphotericin B and flucytosine for four as compared with six weeks.

One hundred ninety-four patients with cryptococcal meningitis were enrolled in a multicenter, prospective, randomized clinical trial to compare the efficacy and toxicity of four as compared with six weeks of combination amphotericin B and flucytosine therapy. Among 91 patients who met preestablished criteria for randomization, cure or improvement was noted in 75 percent of those treated for four weeks and in 85 percent of those treated for six weeks. The estimated relapse rate for the four-week regimen was higher--27 as compared with 16 percent--whereas the incidence of toxic effects for the two regimens was similar--44 as compared with 43 percent. Among 23 transplant recipients, 4 of 5 treated for four weeks relapsed, leading to the decision to treat the rest of the group for six weeks. Only 3 of the 18 treated for six weeks relapsed. In a third group of 80 patients, the protocol was not followed during the initial four weeks, and these patients were not randomized. Thirty-eight died or relapsed. Multifactorial analysis of pretreatment factors for all 194 patients identified three significant predictors (P less than 0.05) of a favorable response: headache as a symptom, normal mental status, and a cerebrospinal fluid white-cell count above 20 per cubic millimeter. These and other findings in this study are consistent with the view that the four-week regimen should be reserved for patients who have meningitis without neurologic complications, underlying disease, or immunosuppressive therapy; a pretreatment cerebrospinal fluid white-cell count above 20 per cubic millimeter and a serum cryptococcal antigen titer below 1:32; and at four weeks of therapy, a negative cerebrospinal fluid India ink preparation and serum and cerebrospinal fluid cryptococcal-antigen titers below 1:8. Patients who do not meet these criteria should receive at least six weeks of therapy.

Adolescent↗
PubMed1987

Fungal endocarditis complicating treatment of prosthetic valve bacterial endocarditis: value of prophylactic oral nystatin.

We describe two patients in whom fungal endocarditis occurred during antibiotic therapy for prosthetic valve bacterial endocarditis. Successful management of both patients was eventually achieved with antifungal therapy and replacement of the prosthetic valves. These cases and review of the literature suggest that (1) high-dose antibacterial therapy predisposes to fungal endocarditis; (2) during prolonged antibiotic therapy in patients predisposed to endocarditis, clinicians should consider the use of oral nystatin as prophylaxis against fungemia and possible fungal endocarditis; and (3) early replacement of prosthetic valves infected with fungi is indicated because chemotherapy alone is predictably inadequate to effect a cure.

Adult↗
PubMed1985

Invasive aspergillosis of the sphenoid sinus manifested as a pituitary tumor.

Aspergillus infection of the paranasal sinuses is rare but is the most common fungal infection of these structures and should be suspected when sinusitis does not respond to antibacterial drugs. Our case involved the sphenoid sinus, and was initially thought to be a nonfunctioning pituitary tumor. Treatment of Aspergillus sinusitis principally involves surgical debridement, reestablishment of aeration and drainage of the involved sinuses, and adjunctive antifungal chemotherapy.

Aspergillosis↗
PubMed1985

Cutaneous chromomycosis in renal transplant recipients. Successful management in two cases.

Cutaneous chromomycosis occurred in two renal transplant recipients from the south central United States. Both patients have been managed successfully with surgical excision of isolated lesions, and the condition of one of these has been improved but not cured with low-dose ketoconazole therapy. Even in the immunocompromised host, localized cutaneous chromomycosis may not require more aggressive systemic antifungal chemotherapy.

Abscess↗
PubMed1984

Campylobacter fetus ssp fetus cholecystitis and relapsing bacteremia in a patient with acquired immunodeficiency syndrome.

Acute gangrenous cholecystitis and relapsing bacteremia caused by Campylobacter fetus ssp fetus occurred in a patient with acquired immunodeficiency syndrome. Biliary tract colonization probably accounted in part for this unusual phenomenon. Whether the patient's deficiency of cell-mediated immunity contributed to his disease is not known.

Acquired Immunodeficiency Syndrome↗
PubMed1983

Treatment of systemic mycoses with ketoconazole: emphasis on toxicity and clinical response in 52 patients. National Institute of Allergy and Infectious Diseases collaborative antifungal study.

The pharmacology, in vitro mycologic activity, toxicity, and efficacy of ketoconazole were studied in a Phase-II evaluation by the National Institutes of Health and National Institute of Allergy and Infectious Disease Mycoses Study Group. This report emphasizes the toxicity and clinical response data in 52 patients with the following systemic mycoses: blastomycosis in 16 patients; nonmeningeal coccidioidomycosis in 13; histoplasmosis in 8; nonmeningeal cryptococcosis in 7; sporotrichosis in 7; and both blastomycosis and nonmeningeal coccidioidomycosis in 1. Maximum daily doses of ketoconazole were 100 mg in 1 patient; 200 mg in 23; 400 mg in 12; and 600 mg in 16. In 52% of the patients, duration of therapy ranged from less than 1 to 6 months, whereas in 35%, duration ranged from 7 to 12 months, and in 13%, from 12 to 22 months. In 35 patients (67%), evidence of toxicity was not seen. Nausea, anorexia, or vomiting occurred in 21%. Cure or marked improvement was shown in 27 patients (52%), whereas failure of the primary course was seen in 14 (27%) and relapse after ketoconazole was discontinued in 11 (21%). Although this evaluation did not provide clear-cut clinical response data, our results indicate that ketoconazole, in the dosage regimens used, was more effective in patients with histoplasmosis and nonmeningeal cryptococcosis than in patients with blastomycosis and nonmeningeal coccidioidomycosis, and least effective in patients with sporotrichosis.

Adolescent↗
PubMed1982

Attachment of pathogenic Neisseria to human mucosal surfaces: role in pathogenesis.

Studies of the interaction between Neisseria gonorrhoeae and human fallopian tube mucosa in organ culture suggest that attachment of gonococci is important, not only to secure th organism in the host, but also to initiate the disease process. The steps observed in gonococcal infection of fallopian tube organ cultures are: 1) attachment of gonococci to microvilli of nonciliated cells; 2) release from gonococci of lipopolysaccharide and possibly other toxic moities to cause mucosa damage; 3) engulfment or phagocytosis of gonococci by nonciliated cells; 4) transport of phagocytic vacuoles containing gonococci to the base of the nonciliated cells; and 5) exocytosis of gonococci within phagocytic vacuoles into the subepithelial tissues. In vivo, these steps might result in extensive local disease (e.g. salpingitis) or in the invasion of blood vessels to cause disseminated disease. Preliminary studies of human nasopharyngeal tissue in organ culture infected with Neisseria meningitidis indicate that meningococci attach to microvilli of nonciliated cells and are phagocytized by these cells. Meningococci subsequently appear in subepithelial tissues, though the route they take is not yet certain. These observations suggest at least some of the ways in which attachment may play a role in disease caused by N. gonorrhoeae and N. meningitidis. Mechanisms to block this attachment may provide new approaches to the prevention of infections caused by the pathogenic Neisseria.

Epithelium↗
PubMed1981

The problem of bacillus species infection with special emphasis on the virulence of Bacillus cereus.

Although Bacillus cereus is an uncommon ocular pathogen, infection with it usually results in loss of the eye. Although previous reports have emphasized endogenous infection, our recent experience indicates the importance of B cereus infection following trauma. Management is hampered by ineffectiveness of current empirical antibiotic regimens. This microorganism is resistant to both the penicillins and the cephalosporins. Although B cereus is susceptible to gentamicin, our studies indicate that gentamicin by itself is inadequate to eradicate the infection. B cereus, however, is susceptible to clindamycin and combined therapy with gentamicin and clindamycin appears to offer the best approach. Early diagnosis is the key to successful treatment. We believe the clinical circumstances likely to lead to B cereus infection, as well as the manifestations of the disease itself, are sufficiently distinctive to alert the ophthalmologist to the possibility of this infection. Prompt recognition of the infection should allow institution of appropriate therapy before permanent structural changes occur.

Abscess↗
PubMed1981

Studies of toxicity of Neisseria gonorrhoeae for human fallopian tube mucosa.

Infection of human fallopian tubes in organ culture with Neisseria gonorrhoeae causes extensive damage of the mucosa. Filter-sterilized supernatant from gonococci-infected organ cultures produced similar damage in recipient uninfected organ cultures. This observation indicated the presence of one or more toxic factors. The toxic activity was unchanged after heating the supernatant to 85 C and was only partially diminished by dialysis. Toxic activity could not be detected in homogenates of uninfected organ cultures but was present in supernatants of gonococcal broth cultures. Toxic supernatants from organ cultures contained microgram quantities of gonococcal lipopolysaccharide (LPS). Amounts of this LPS and toxic activity for genital mucosa were both substantially reduced by absorption of the supernatant with limulus amoebocyte lysate. Thus, gonococcal LPS appears to be responsible for most of the toxicity of filter-sterilized supernatant from gonococci-infected human fallopian tubes in organ culture and may play an important role in the pathogenesis of gonococcal infection in vivo.

Cilia↗